The Potential Applications of Stem Cell Conditioned Medium Secretome in Knee Cartilage Regeneration: A Systematic Review
Downloads
Background: Articular cartilage injuries often result from trauma, genetic predisposition, and degeneration. These injuries lack inherent regeneration mechanisms due to the absence of blood vessels and limited progenitor cell entry. Osteoarthritis is characterized by gradual cartilage deterioration. Mesenchymal stem cells (MSCs), particularly their secretome including exosomes, hold promise as a regenerative therapy. This review explores the application of MSCs and their secretome to address cartilage defects.
Methods: This review was conducted based on PRISMA guidelines. Animal model studies focusing on the use of stem cell secretomes for cartilage regeneration were explored. The search, encompassing PubMed, MEDLINE, the Cochrane Library, Scopus, Web of Science, and Science Direct from January 10, 2023, to July 27, 2023, was conducted utilizing Google Chrome as the search engine. Studies with outcomes based on OARSI or ICRS scores, as well as any additional outcomes related to MSC secretome utilization, cartilage regeneration, and proliferation, were included.
Results: Our systematic review identified six studies using MSCs in vivo and in vitro. Synovial membrane-derived MSCs significantly enhanced cartilage regeneration by elevating chondrogenic capabilities. Hydrogel-based systems techniques and 3D-printed scaffolds have emerged for innovative delivery. Specific microRNAs, such as miR-92a-3p, have been recognized for enhancing cartilage regeneration. Strategies for the effective targeting of MSC exosomes to the precise cartilage damage site have been explored.
Conclusions: The studies demonstrate the potential of MSC-derived secretomes and exosomes for knee cartilage regeneration in animal models. Further research and clinical trials are needed to refine these approaches for practical application.
Conforti A, Scarsella M, Starc N, Giorda E, Biagini S, Proia A, et al. Microvescicles derived from mesenchymal stromal cells are not as effective as their cellular counterpart in the ability to modulate immune responses in vitro. Stem Cells Dev 2014;23(21):2591–9.
Blazquez R, Sanchez-Margallo FM, de la Rosa O, Dalemans W, Ãlvarez V, Tarazona R, et al. Immunomodulatory potential of human adipose mesenchymal stem cells derived exosomes on in vitro stimulated T cells. Front Immunol 2014;5:556.
Diomede F, D’Aurora M, Gugliandolo A, Merciaro I, Orsini T, Gatta V, et al. Biofunctionalized scaffold in bone tissue repair. Int J Mol Sci 2018;19(4):1022.
Bousnaki M, Bakopoulou A, Kritis A, Koidis P. The efficacy of stem cells secretome application in osteoarthritis: A systematic review of in vivo studies. Stem Cell Rev Rep 2020;16(6):1222–41.
Freitag J, Bates D, Wickham J, Shah K, Huguenin L, Tenen A, et al. Adipose-derived mesenchymal stem cell therapy in the treatment of knee osteoarthritis: a randomized controlled trial. Regenerative Med 2019;14(3):213–30.
Lee WS, Kim HJ, Kim KI, Kim GB, Jin W. Intra-articular injection of autologous adipose tissue-derived mesenchymal stem cells for the treatment of knee osteoarthritis: A phase IIb, randomized, placebo-controlled clinical trial. Stem Cells Transl Med 2019;8(6):504–11.
Matas J, Orrego M, Amenabar D, Infante C, Tapia-Limonchi R, Cadiz MI, et al. Umbilical cord-derived mesenchymal stromal cells (MSCs) for knee osteoarthritis: Repeated MSC dosing is superior to a single MSCdose and to hyaluronic acid in a controlled randomized phase I/II trial. Stem Cells Transl Med 2019;8(3):215–24.
Kim YS, Choi YJ, Koh YG. Mesenchymal stem cell implantation in knee osteoarthritis. Am J Sports Med 2015;43(9):2293–301.
Ni Z, Zhou S, Li S, Kuang L, Chen H, Luo X, et al. Exosomes: roles and therapeutic potential in osteoarthritis. Bone Res 2020;8(1):25.
Moher D, Liberati A, Tetzlaff J, Altman DG; PRISMA Group. Preferred reporting items for systematic seviews and meta-analyses: The PRISMA statement. Ann Intern Med 2009;151(4):264-9.
Lubis AMT, Aprianto P, Pawitan JA, Priosoeryanto BP, Dewi TIT, Kamal AF. Intra-articular injection of secretome, derived from umbilical cord mesenchymal stem cell, enhances the regeneration process of cartilage in early-stage osteo-arthritis: an animal study. Acta Orthop 2023;94:300–6.
Zhu Y, Wang Y, Zhao B, Niu X, Hu B, Li Q, et al. Comparison of exosomes secreted by induced pluripotent stem cell-derived mesenchymal stem cells and synovial membrane-derived mesenchymal stem cells for the treatment of osteoarthritis. Stem Cell Res Ther 2017;8(1):64.
Liu X, Yang Y, Li Y, Niu X, Zhao B, Wang Y, et al. Integration of stem cell-derived exosomes with in situ hydrogel glue as a promising tissue patch for articular cartilage regeneration. Nanoscale 2017;9(13):4430–8.
Mao G, Zhang Z, Hu S, Zhang Z, Chang Z, Huang Z, et al. Exosomes derived from miR-92a-3p-overexpressing human mesenchymal stem cells enhance chondrogenesis and suppress cartilage degradation via targeting WNT5A. Stem Cell Res Ther 2018;9(1):247.
Wu J, Kuang L, Chen C, Yang J, Zeng WN, Li T, et al. miR-100-5p-abundant exosomes derived from infrapatellar fat pad MSCs protect articular cartilage and ameliorate gait abnormalities via inhibition of mTOR in osteoarthritis. Biomaterials 2019;206:87–100.
Chen Q, Liang Q, Zhuang W, Zhou J, Zhang B, Xu P, et al. Tenocyte proliferation and migration promoted by rat bone marrow mesenchymal stem cell-derived conditioned medium. Biotechnol Lett 2018;40(1):215–24.
Chen P, Zheng L, Wang Y, Tao M, Xie Z, Xia C, et al. Desktop-stereolithography 3D printing of a radially oriented extracellular matrix/mesenchymal stem cell exosome bioink for osteochondral defect regeneration. Theranostics 2019;9(9):2439–59.
Li J, Hosseini-Beheshti E, Grau G, Zreiqat H, Little C. Stem cell-derived extracellular vesicles for treating joint injury and osteoarthritis. Nanomaterials 2019;9(2):261.
Zhou Q, Cai Y, Jiang Y, Lin X. Exosomes in osteoarthritis and cartilage injury: advanced development and potential therapeutic strategies. Int J Biol Sci 2020;16(11):1811–20.
Balbi C, Piccoli M, Barile L, Papait A, Armirotti A, Principi E, et al. First Characterization of human amniotic fluid stem cell extracellular vesicles as a powerful paracrine tool endowed with regenerative potential. Stem Cells Transl Med 2017;6(5):1340–55.
Wang KX, Xu LL, Rui YF, Huang S, Lin SE, Xiong JH, et al. The effects of secretion factors from umbilical cord derived mesenchymal stem cells on osteogenic differentiation of mesenchymal stem cells. PLoS One 2015;10(3):e0120593.
Copyright (c) 2024 Journal Orthopaedi and Traumatology Surabaya
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
- The author acknowledges that the copyright of the article is transferred to the Journal of Orthopaedi and Traumatology Surabaya (JOINTS), whilst the author retains the moral right to the publication.
- The legal formal aspect of journal publication accessibility refers to Creative Commons Attribution-Non Commercial-Share Alike 4.0 International License (CC BY-NC-SA).
- All published manuscripts, whether in print or electronic form, are open access for educational, research, library purposes, and non-commercial uses. In addition to the aims mentioned above, the editorial board is not liable for any potential violations of copyright laws.
- The form to submit the manuscript's authenticity and copyright statement can be downloaded here.
Journal of Orthopaedi and Traumatology Surabaya (JOINTS) is licensed under a Creative Commons Attribution-Non Commercial-Share Alike 4.0 International License.